Instructions Nicergoline film-coated tablets 10 mg blister No. 30
Composition
active ingredient: nicergoline;
1 tablet contains nicergoline – 10 mg;
Excipients: lactose, monohydrate; magnesium carbonate heavy; stearic acid; potato starch; sugar; talc; titanium dioxide (E 171); povidone; colloidal anhydrous silicon dioxide; white wax.
Dosage form
Film-coated tablets.
Main physicochemical properties: white film-coated tablets. Two layers are visible in cross-section.
Pharmacotherapeutic group
Peripheral vasodilators. Ergot alkaloids.
ATX code C04A E02.
Pharmacological properties
Pharmacodynamics.
Nicergoline is an ergoline derivative with alpha-1-adrenergic blocking activity when administered parenterally. After oral administration, nicergoline undergoes rapid and extensive metabolism to form a number of metabolites, which also exert activity at various levels of the central nervous system.
When administered orally, Nicergoline exhibits numerous neuropharmacological effects: it not only increases glucose uptake and consumption in the brain, enhances protein and nucleic acid biosynthesis, but also affects various neurotransmitter systems.
Nicergoline improves cerebral cholinergic functions in old animals. Long-term administration of nicergoline in old rats prevented the age-related decline in acetylcholine levels (in the cortex and striatum) and reduced acetylcholine release (in the hippocampus) in vivo. After long-term oral administration of nicergoline, an increase in choline acetyltransferase activity and muscarinic receptor density was also observed. Moreover, in in vitro and in vivo studies, nicergoline significantly increased acetylcholinesterase activity. In these experimental studies, neurochemical effects were observed simultaneously with a stable improvement in behavioral responses, for example, in the maze test in mature animals that were administered nicergoline for a long time, the development of responses similar to those in young animals was observed.
Nicergoline has also been shown to reduce cognitive impairment induced by several agents (hypoxia, electroconvulsive therapy (ECT), scopolamine) in animals. Oral administration of nicergoline at low doses increases dopamine metabolism in mature animals, particularly in the mesolimbic region, likely by modulating dopaminergic receptors. Nicergoline improves signal transduction mechanisms in cells in mature animals. Both after a single and long-term oral administration of the drug, an increase in basal and agonist-sensitive phosphoinositide metabolism was observed. Nicergoline also increases the activity and translocation of calcium-dependent protein kinase C isoforms to the membrane. Due to its antioxidant effect and ability to activate detoxification enzymes, nicergoline prevents neuronal cell death caused by oxidative stress and apoptosis. Nicergoline attenuates the age-related decrease in neuronal nitric oxide synthase mRNA expression, which may also contribute to improving cognitive function.
Pharmacokinetics.
After oral administration, nicergoline is rapidly and almost completely absorbed. The maximum radioactivity after administration of low doses (4–5 mg) of H-labeled nicergoline to healthy volunteers was determined after 1.5 hours. However, after oral administration of therapeutic doses (30 mg) of C-labeled nicergoline to healthy volunteers, the maximum radioactivity in serum was observed 3 hours after dosing. After oral administration of nicergoline (15 mg) to healthy volunteers, the area under the curve of serum radioactivity was 81% and 6% of the value calculated for the two main metabolites of nicergoline - MDL and MMDL, respectively. Peak plasma concentrations of MDL were reached approximately 3–5 hours after single or multiple administration of a 30 mg tablet. Peak plasma concentrations of MMDL were reached approximately 0.5–1 hour after single administration of a 30 mg tablet.
The distribution of the drug in tissues is rapid and extensive, as reflected by the short distribution phase of serum radioactivity. The volume of distribution of nicergoline in the central compartment (approximately calculated by dividing the dose by the plasma nicergoline concentration in the first sampling period after intravenous administration of a nominal dose of 2 mg) is relatively high (224 l), potentially reflecting the distribution of nicergoline in blood cells and/or tissues. Nicergoline is extensively bound to human plasma proteins, with an affinity for α-acid glycoprotein four times higher than for serum albumin. The percentage of binding is relatively constant when the concentration of nicergoline increases from 1 μg/ml to 500 μg/ml. Both metabolites of nicergoline, MDL and MMDL, are characterized by low levels of binding, approximately 14.7% and 34.7%, respectively, in the concentration range of 50–200 ng/ml. The drug is excreted predominantly in the urine. Within 120 hours after administration, approximately 82% of the total amount of radiolabeled nicergoline is excreted by the kidneys, and 10% in the feces. Nicergoline undergoes extensive metabolism, mainly by hydrolysis of ester bonds to form MMDL, and then MDL by demethylation (catalytically mediated by the CYP2D6 isoenzyme). Therefore, the pharmacokinetics of nicergoline and its metabolites are affected in patients with a genetic deficiency of CYP2D6. The active metabolites formed (MMDL and MDL) are conjugated with glucuronic acid. The major metabolite MDL accounts for 51% of the total dose and 76% of the radioactivity recovered in urine after a 15 mg oral dose. The mean terminal elimination half-life of MDL is in the range of approximately 11–20 hours.
The effect of renal impairment on the pharmacokinetics of nicergoline was evaluated in patients with mild (creatinine clearance (Clcr) 60–80 mL/min), moderate (Clcr 30–50 mL/min) and severe (Clcr 10–25 mL/min) renal impairment. In patients with mild (n=5), moderate (n=5) and severe (n=4) renal impairment, significant differences were observed in the amount of MDL excreted in the urine within 120 hours after oral administration of nicergoline at a dose of 30 mg (38.1%, 42.6% and 25.7% of the administered dose, respectively); for MMDL, the corresponding values were 1.7%, 0.6% and 0.2%. In patients with severe renal impairment, a significant decrease in the excretion of MDL in the urine was determined compared to the other two groups. In addition, patients with mild, moderate, or severe renal impairment had a mean decrease in urinary MDL excretion (0-72 hours) of 32%, 32%, and 59%, respectively, compared to patients with normal renal function in another study using the 30 mg tablet.
The pharmacokinetics of nicergoline in patients with impaired liver function have not been studied.
The pharmacokinetics of nicergoline have not been studied in children.
The effect of age (in elderly patients) on the pharmacokinetics of nicergoline has not been fully studied.
Indication
Acute and chronic cerebrovascular metabolic disorders due to atherosclerosis, thrombosis and embolism of cerebral vessels, transient disorders of cerebral circulation (transient ischemic attacks).
Headache.
As an adjunctive therapy for systemic arterial hypertension.
Contraindication
Hypersensitivity to ergot alkaloids or to any other component of the drug. Recent myocardial infarction, acute bleeding, orthostatic hypotension, severe bradycardia.
Interaction with other medicinal products and other types of interactions
The drug is used with caution in combination with:
antihypertensive agents: nicergoline may enhance their effect. Nicergoline may enhance the effect of beta-blockers on the heart;
sympathomimetics (alpha- and beta-): nicergoline may have an antagonistic effect on the vasoconstrictor effect of sympathomimetic agents due to blocking alpha-adrenergic receptors;
medicinal products metabolized by the CYP2D6 isoenzyme: since nicergoline is metabolized by the CYP2D6 isoenzyme, the possibility of interactions with other medicinal products metabolized by the same pathway cannot be excluded;
antiplatelet agents and anticoagulants (e.g. acetylsalicylic acid): enhances the effect on hemostasis, which may increase bleeding time;
Drugs that affect uric acid metabolism: nicergoline may lead to an asymptomatic increase in uric acid concentrations in blood plasma.
Application features
Studies with single or multiple administration of nicergoline have shown that nicergoline can reduce systolic blood pressure and, to a much lesser extent, diastolic blood pressure in normotensive and hypertensive patients. These effects may vary, as other studies have not shown changes in systolic or diastolic blood pressure.
The drug should be used with caution in patients with exertional angina and severe atherosclerosis. At the beginning of treatment, orthostatic hypotension may develop.
The drug should be used with caution in patients with a history of hyperuricemia or gout and/or during concomitant treatment with drugs that may affect the metabolism and excretion of uric acid.
The development of fibrosis (e.g., pulmonary, cardiac, valvular, and retroperitoneal fibrosis) has been associated with the use of certain ergot alkaloids, which possess agonist activity at serotonin 5-HT2β receptors.
Symptoms of ergotism (including nausea, vomiting, diarrhea, abdominal pain, and peripheral vasoconstriction) have been reported with the use of some ergot alkaloids and their derivatives.
Before prescribing this class of medications, doctors need to be familiar with the signs of ergot overdose.
The drug should not be used in patients with hereditary galactose intolerance, lactase deficiency or glucose/galactose malabsorption syndrome.
Use during pregnancy or breastfeeding
Nicergoline has no toxic effect on the reproductive function of pregnant rats and rabbits. Clinical studies involving pregnant women have not been conducted.
Given the indications of Nicergoline, its use by pregnant and breastfeeding women is unlikely. During pregnancy, Nicergoline should be used only in cases where the potential benefit to the patient outweighs the potential risk to the fetus.
Breast-feeding.
It is not known whether nicergoline passes into breast milk, so nicergoline should not be used by women who are breastfeeding.
Fertility.
Nicergoline does not affect the fertility of rats.
Ability to influence reaction speed when driving vehicles or other mechanisms
Although the clinical effects of the drug nicergoline are used to improve attention and concentration, its effect on the ability to drive vehicles and other automated systems has never been studied. In any case, caution should be exercised, taking into account the underlying disease of the patients. When driving vehicles or working with other automated systems, it should be taken into account that dizziness or drowsiness may occasionally occur (see section "Adverse reactions").
Method of administration and doses
The recommended daily dose of the drug is 5–10 mg three times a day at equal intervals, preferably between meals, for continuous treatment.
Dosage regimens, duration of treatment, and route of administration depend on the severity of individual clinical manifestations of the disease.
According to the results of pharmacokinetic and tolerability studies, no dose adjustment is required for elderly patients.
Patients with renal impairment.
Since renal excretion is the main route of elimination (80%) of nicergoline and its metabolites, a dose reduction is recommended for patients with impaired renal function (serum creatinine ≥ 2 mg/ml).
The effect of treatment appears gradually. Since therapy is usually carried out over a long period of time, the doctor should assess the feasibility of continuing treatment at least every 6 months.
Children. The drug should not be used in children.
Overdose
When using high doses of nicergoline, a temporary decrease in blood pressure may be observed. Usually, this condition does not require special treatment - it is enough to put the patient in a supine position for a few minutes. In exceptional cases of insufficient cerebral and cardiac blood supply, it is advisable to use sympathomimetics and constant monitoring of blood pressure indicators.
Side effects
The frequency categories are expressed as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); frequency unknown (frequency cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Psychiatric disorders: Uncommon: agitation, confusion, insomnia.
Nervous system disorders: Uncommon: drowsiness, dizziness, headache; frequency unknown: feeling hot*.
Vascular disorders: Uncommon: hypotension, flushing.
Gastrointestinal disorders: Common: abdominal discomfort; uncommon: diarrhea, nausea, constipation.
Skin and subcutaneous tissue disorders: Uncommon: pruritus; frequency unknown: rash*.
General disorders and administration site conditions: Frequency not known: fibrosis*.
Research findings: Uncommon: increased blood uric acid concentration.
There is evidence of increased blood uric acid levels.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions in the post-marketing period is an important measure. This allows for continued monitoring of the benefit/risk balance of the drug. Healthcare professionals are asked to report any suspected adverse reactions in accordance with legal requirements.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister, 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Halychpharm".
Address
Ukraine, 79024, Lviv, Opryshkivska St., 6/8.
